Fruits, Vegetables Ease Metabolic Acidosis

A healthy diet may be a cost-effective way for CKD patients to manage a potentially serious abnormality

BY JOHN SCHIESZER DIETARY ACID REDUCTION with fruits and vegetables (F+V) or sodium bicarbonate supplements appear to produce comparable improvements in metabolic acidosis, but F+V may produce even greater improvements in several measured health outcomes in patients with chronic kidney disease (CKD) stage 3, according to a new post hoc analysis of data from a previously published clinical trial. The analysis also showed that F+V can produce improved health outcomes cost-effectively.

Previous studies have shown that F+V can effectively treat metabolic acidosis and slow progression of CKD. In addition, adding F+V to diets of patients with CKD can improve their cardiovascular disease (CVD) risk profile similar to what has been shown in non-CKD populations.

The new analysis included 108 macroalbuminuric patients with nondiabetic CKD stage 3 who had metabolic acidosis. Investigators randomly assigned patients to receive either F+V in amounts calculated to reduce dietary acid by half, oral sodium bicarbonate supplements, or usual care. They assessed patients annually for 5 years and calculated a mean overall health score based on plasma total CO2, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, change in medication dose, estimated glomerular filtration rate, and systolic blood pressure. The investigators, led by Donald E. Wesson, MD, professor of medicine at Texas A&M University College of Medicine in Dallas, also analyzed the number of cardiovascular disease (CVD) events, medication costs, and hospitalization costs.

Same Effects on Plasma CO2 The study showed that the net plasma total CO2 increase at 5 years was the same for the sodium bicarbonate group and the F+V group. Average health scores at 5 years favored the F+V group. No CVD events occurred in the F+V group, 2 occurred in the sodium bicarbonate group, and 6 occurred in the usual care group, Dr Wesson and his colleagues reported in the Journal of Renal Nutrition. The investigators observed no differences in the total 5-year household costs per beneficial health outcome between the F+V group and sodium bicarbonate group. The usual care group had the highest household costs per beneficial health outcome.

“We were able to ascertain the costeffectiveness of the F+V intervention by looking at the overall population, not at individual participants,” Dr Wesson told Renal & Urology News. “The latter has implications that extend into policy as to what treatments we recommend for chronic diseases, in this case CKD.”

Drugs Should Be Adjunctive to Diet Further, he stated that diet should be considered foundational to the management of patients with CKD because of its potential to reduce mortality and morbidity. “Drugs should be considered adjunctive to diet,” Dr Wesson said. “Our current approach in the medical community is typically drugs first then diet added as adjunctive therapy if additional benefits are needed. The understandable challenge is to get patients to change their diets, something that we all recognize is very difficult to do.”

Clinicians should attempt to educate patients with CKD and their caregivers about the importance and benefits of dietary management of CKD, he added.

Jerry Yee, MD, chief of nephrology and hypertension at Henry Ford Hospital in Detroit, Michigan, called the findings of the new study highly relevant. “Many physicians would fear that the higher fresh fruits and vegetables diet would cause hyperkalemia. This did not occur,” Dr Yee said.

Sufficient data on the effectiveness of diets rich in fruits and vegetables in controlling metabolic acidosis are available to support widespread use of this approach, especially because such diets are healthier overall, he said.

Dr Yee pointed out that patients in the usual care group fared worse than those receiving sodium bicarbonate supplements, even though the sodium bicarbonate prescription was somewhat less than what is normally administered by nephrologists who do not prescribe F+V diets for patients with CKD and

Clinicians should try to educate patients with chronic kidney disease and their caregivers about the importance and benefits of dietary management, investigator says.

metabolic acidosis.

Nephrologist Leighton R. James, MD, of the Medical College of Georgia at Augusta University in Augusta, Georgia, said he has some concerns about the current study because of its design. The study did not clearly show that the amount of bicarbonate received from F+V was equivalent to that received from sodium bicarbonate tablets, Dr James said. “This is important as several fruits in the F+V group contain citrate, which is converted to bicarbonate,” he explained. “Each citrate molecule generates 3 molecules of bicarbonate. So, the study would have to show that the amount of bicarbonate supplied by each intervention was equivalent.”

In response, Dr Wesson said his team did match the amount of alkali being given in the F+V and sodium bicarbonate participant groups. “Not only was that the study design, this is supported by the fact that the net serum total CO2 intake was nearly identical between the F+V and sodium bicardonate groups, supporting that they received the same amount of alkali.”

Because the study could not be blinded, Dr James said, participants would know what they are receiving, and this could change their behavior. For example, participants might increase their physical activity or consume fewer calories, possibly contributing to a lower body mass index in the F+V group.

Sodium from Sodium Bicarbonate In addition, he noted, the study did not control for the effect of sodium from sodium bicarbonate supplements, which can impact blood pressure. “The differences in blood pressure and need for blood pressure medications may be related to sodium intake rather the F+V, which typically has more potassium and less sodium,” Dr James said. In terms of overall health score, the reduction in medication was considered as an improvement. However, he said it is not clear that the observed reduction was directly related to F+V or not controlling for other factors such as fat intake and the quantity of bicarbonate ingested.

Dr Wesson noted that the statistical analysis did not account for fat intake among the 3 groups.

Nephrologist Christopher Passero, MD, clinical assistant professor of medicine in the Renal-Electrolyte Division at the University of Pittsburgh in Pittsburgh, Pennsylvania, said the findings from the new study are similar those from prior studies suggesting that an alkali-producing F+V diet can achieve the same effects as alkali therapy to correct the metabolic acidosis seen in patients with CKD.

The meat-rich, high-protein diets common in the United States contribute to acid production, he said. Dietary modification involving increasing the proportion of fruits and vegetables could help individuals reduce daily protein intake. Generally, for patients with CKD, nephrologists recommend reducing protein intake to 0.6–0.8 g per kg body weight (which is about 2 portions of meat, 3 ounces each, per day for most people, or in the case of the current study, a vegetable equivalent), Dr Passero said. “It would be helpful if future studies described other considerations regarding diet, including sustainability, and avoidance of micronutrient and protein malnutrition.” ■

Hospitals turned to PD

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renal recovery by the time of discharge. Eight patients remained hospitalized, and none remained on PD. Four patients were switched to either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD), and 4 patients had renal recovery and no longer needed RRT.

Advantages Dr Sourial’s team noted that PD use in the AKI setting has advantages, including no need for vascular access, reduced cost compared with CRRT and IHD, and no need for special plumbing to supply water for dialysate for IHD, “allowing for treatment in hospital rooms without adequate water supply.” In addition, staff can be educated to perform PD safely with few resources over a short period of time compared with other dialysis modalities.

“Based on our experience, urgent PD is a feasible RRT option to treat patients with COVID-19 and AKI,” the authors concluded.

A dramatic surge in ICU patients with COVID-19-related AKI also prompted Bellevue Hospital Center to institute an acute PD program. “Our ability to provide RRT with CVVH [continuous veno-venous hemofiltration] and IHD was severely limited by critical shortages of equipment and personnel,” Nina J. Caplin, MD, and colleagues concluded in a slide presentation.

KTRs and COVID-19

continued from page 1 the 145 patients, 55% were older than 60 years and 65% were male. The median time since receiving a transplant was 5 years; only 16% had received a transplant less than 1 year from presentation.

Common symptoms at COVID-19 onset were fever and dyspnea (71%), myalgia (54%), and diarrhea (35%). During hospitalization, 83% of patients received hydroxychloroquine, 76% antibiotics, 13% tocilizumab, and 10% antivirals.

Hypertension was the most common comorbidity (95%), followed by obesity, heart disease, and lung disease, which were present in 41%, 25%, and 19% of patients, respectively.

The study by Northwell investigators examined data from 30 KTRs hospitalized with COVID-19. Death risk was higher if patients were admitted to a non-transplant hospital (80% vs 23%), lymphopenic at presentation (47%

In addition, patients with COVID-19 had increased clotting of membranes, circuits, and lines, at times rendering patients unable to tolerate and receive CVVH and/or IHD, they noted. “Acute PD more than adequately filled the gap in treatment options during this unprecedented crisis.”

As of May 8, 39 patients received PD catheters and 36 of them PD. Of these, 20 died in less than 30 days; 15 survived for more than 30 days, and 8 of them recovered renal function. One patient had long-term end-stage kidney disease (ESKD) and lost all vascular access. That patient survived.

Rapid adoption of PD during the pandemic could encourage wider use of the modality.

“Our experience provides a roadmap for responses to future crises with heavy burdens of AKI,” Dr Caplin and colleagues concluded.

Also during the conference, Elly Varma, MBBS, and colleagues at Weill Cornell Medicine, reported their experience with the use of acute PD for 11 patients with COVID-19-related AKI that required RRT. The patients had undergone bedside PD catheter placement from April 1 to April 30.

The median time from AKI to PD catheter insertion was 5 days. At 1 week, vs 8%), and had an oxygen saturation less than 94% on admission (100% vs 57%), Dr Vinay and colleagues reported.

During hospitalization, mortality also was higher among patients with elevated peak serum creatinine (3.2 vs 1.5 mg/dL), or if they required intubation (70% vs 14%). Increases in inflammatory markers, including peak D-dimer, peak C-reactive protein, ferritin, and procalcitonin, also predicted mortality.

The study population was 61% male, 32% White, and 29% Black. The most common symptom was cough, followed by fever, shortness of breath, and fatigue. Ten patients required ventilation. Most patients were on triple immunosuppression (94% on tacrolimus, 90% on mycophenolate, and 74% on prednisone). With respect to treatment, 93% of patients received hydroxychloroquine, 50% received azithromycin, 14% received convalescent plasma, and 10% received an interleukin-6 inhibitor. One patient received the antiviral remdesivir. ■ 10 catheters (91%) were functional with no leaks or bleeding detected. Only 1 patient was switched to CRRT due to primary PD catheter nonfunction. The median duration of follow-up from time of PD catheter insertion was 37 days. Of the 11 patients, 4 (36%) died, 5 (45%) had recovery of renal function, and 2 (18%) were alive and on HD.

“We hypothesize that preservation of residual renal function utilizing PD may have contributed to the high rate of renal recovery observed,” the authors concluded.

The rapid embrace of PD to address an explosive demand for dialysis brought on by the COVID-19 pandemic could contribute to increased uptake of the modality generally, according to Virginia Wang, PhD, MSPH, of Duke University School of Medicine in Durham, North Carolina, a coauthor of the study titled “Trends in Peritoneal Dialysis Use in the United States After Medicare Payment Reform,” which was published in 2019 in the Clinical Journal of the American Society of Nephrology.

Noting that uptake of PD has risen only moderately in the last few decades, she said, “I’ve wondered whether and what kind of system shocks would propel faster growth in PD use. The COVID-19 pandemic may be one of them, as suggested by these case reports of hospitals’ experiences initiating acute PD programs for patients with COVID-related AKI.”

Only a small minority of patients with ESKD in the United States receive PD

Voclosporin use for LN

continued from page 1 the management of patients with lupus nephritis.”

Dr Rovin and colleagues analyzed combined data from the phase 2 AURA-LV and phase 3 AURORA clinical trials. Both trials demonstrated that VCS increased renal response significantly compared with mycophenolate mofetil. They defined renal response as a urine protein-to-creatinine ratio of 0.5 mg/mg or less, an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 or higher or no decline more than 20% from baseline, need for 10 mg prednisone or less 8 weeks prior to endpoint measurements, and no need for rescue medications. The integrated dataset included an intent-to-treat population of 268 patients treated with VCS at a dosage of 23.7 mg twice daily and 266 control patients.

The renal response at 1 year was 43.7% for the VCS arm compared with 23.3% for controls, Dr Rovin’s team reported in as their RRT. As of December 31, 2017, only 7.1% of prevalent ESKD patients in the United States were being treated with PD (compared with 62.7% HD), according to the US Renal Data System 2019 Annual Data Report. Many in the nephrology community say PD is underused.

Why PD Is Underused Many factors in the healthcare delivery system are associated with underuse of PD, including lack of earlier CKD identification and timely preparation for kidney failure, inadequate patient education about all treatment options, and lack of PD availability at dialysis facilities, said Dr Wang, who is an associate professor in the Department of Population Health Sciences and Division of General Internal Medicine. Clinician lack of awareness of, and experience with, PD are commonly cited barriers to wider adoption and use of the modality and may be challenging to address, Dr Wang said. Healthcare providers are unable to get hands-on experience with PD because relatively few patients receive this form of dialysis.

With few alternative solutions, the pandemic forced hospitals to train clinicians, including physicians, nurses, and surgeons, in all facets of PD care and in ways that were probably not well established before COVID-19, Dr Wang said. “In this way, the pandemic could inadvertently represent an opportunity

for PD growth in the US.” ■ a slide presentation. VCS treatment was significantly associated with approximately 2.8-fold increased odds of renal response compared with controls. The 1-year renal response for Hispanic patients — a high-risk LN patient population — was 37.9% for VCS recipients compared with 19.4% for controls.

The largest change in eGFR from baseline for VCS recipients compared with controls occurred early, declining by 5.6 mL/min/1.73 m2 by week 4. By week 52, the change in eGFR improved, declining by 3.7 mL/min/1.73 m2 compared with controls. The mean change from baseline of eGFR in the VCS arm at week 52 was –1.0 mL/min/1.73 m2 , which was not statistically significant.

The proportion of patients who experienced serious adverse events was similar between the VCS and controls groups (22.8% vs 18.8%). ■